The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats

Our recent study demonstrated that the CC-chemokine ligand 2 (CCL2) present in primary afferent fibers (PAFs) plays an important role in the microglia-dependent neuronal activation associated with zymosan-induced inflammatory pain. The present study was aimed to evaluate whether BD1047 (a prototypic...

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Autores principales:	Sungkun Chun, Jun-Ho Lee, Seo-Yeon Yoon, Young-Bae Kwon
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	CCL2 Complete Freund’s adjuvant hyperalgesia microglia sigma-1 receptor Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/e4925015e2d245b2853d27c249cbf970
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spelling	oai:doaj.org-article:e4925015e2d245b2853d27c249cbf9702021-11-11T17:11:34ZThe Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats10.3390/ijms2221117301422-00671661-6596https://doaj.org/article/e4925015e2d245b2853d27c249cbf9702021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11730https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Our recent study demonstrated that the CC-chemokine ligand 2 (CCL2) present in primary afferent fibers (PAFs) plays an important role in the microglia-dependent neuronal activation associated with zymosan-induced inflammatory pain. The present study was aimed to evaluate whether BD1047 (a prototypical sigma-1 receptor (Sig-1R) antagonist) is capable of modifying elevated levels of inflammation-evoked CCL2 as a peripheral antinociceptive mechanism. In DRG primary culture, zymosan dose-dependently increased CCL2 release from isolectin B4 (IB4)-positive DRG neurons, a process that was inhibited by co-culture with BD1047. Single treatment of BD1047 before intraplantar injection of zymosan in rats significantly reduced thermal hyperalgesia and mechanical hyperalgesia, as well as CCL2 expression in DRG neurons and microglia activation in the spinal dorsal horn. In the Complete Freund’s adjuvant (CFA)-induced inflammation model, repeated administration of BD1047 dramatically attenuated thermal hyperalgesia and mechanical hyperalgesia, and significantly diminished CCL2 immunoreactivity and microglia activation. Notably, CFA-induced inflammation significantly increased Sig-1R immunoreactivity in DRG neurons, which was co-localized with CCL2 and IB4, respectively. Taken together, our results suggest that BD1047′s anti-nociceptive property was substantially mediated by the inhibition of CCL2 release in unmyelinated PAFs and that this may, in turn, have attenuated the spinal microglia activation that is associated with inflammatory pain.Sungkun ChunJun-Ho LeeSeo-Yeon YoonYoung-Bae KwonMDPI AGarticleCCL2Complete Freund’s adjuvanthyperalgesiamicrogliasigma-1 receptorBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11730, p 11730 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CCL2 Complete Freund’s adjuvant hyperalgesia microglia sigma-1 receptor Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	CCL2 Complete Freund’s adjuvant hyperalgesia microglia sigma-1 receptor Biology (General) QH301-705.5 Chemistry QD1-999 Sungkun Chun Jun-Ho Lee Seo-Yeon Yoon Young-Bae Kwon The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats
description	Our recent study demonstrated that the CC-chemokine ligand 2 (CCL2) present in primary afferent fibers (PAFs) plays an important role in the microglia-dependent neuronal activation associated with zymosan-induced inflammatory pain. The present study was aimed to evaluate whether BD1047 (a prototypical sigma-1 receptor (Sig-1R) antagonist) is capable of modifying elevated levels of inflammation-evoked CCL2 as a peripheral antinociceptive mechanism. In DRG primary culture, zymosan dose-dependently increased CCL2 release from isolectin B4 (IB4)-positive DRG neurons, a process that was inhibited by co-culture with BD1047. Single treatment of BD1047 before intraplantar injection of zymosan in rats significantly reduced thermal hyperalgesia and mechanical hyperalgesia, as well as CCL2 expression in DRG neurons and microglia activation in the spinal dorsal horn. In the Complete Freund’s adjuvant (CFA)-induced inflammation model, repeated administration of BD1047 dramatically attenuated thermal hyperalgesia and mechanical hyperalgesia, and significantly diminished CCL2 immunoreactivity and microglia activation. Notably, CFA-induced inflammation significantly increased Sig-1R immunoreactivity in DRG neurons, which was co-localized with CCL2 and IB4, respectively. Taken together, our results suggest that BD1047′s anti-nociceptive property was substantially mediated by the inhibition of CCL2 release in unmyelinated PAFs and that this may, in turn, have attenuated the spinal microglia activation that is associated with inflammatory pain.
format	article
author	Sungkun Chun Jun-Ho Lee Seo-Yeon Yoon Young-Bae Kwon
author_facet	Sungkun Chun Jun-Ho Lee Seo-Yeon Yoon Young-Bae Kwon
author_sort	Sungkun Chun
title	The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats
title_short	The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats
title_full	The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats
title_fullStr	The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats
title_full_unstemmed	The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats
title_sort	peripheral role of ccl2 in the anti-nociceptive effect of sigma-1 receptor antagonist bd1047 on inflammatory hyperalgesia in rats
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e4925015e2d245b2853d27c249cbf970
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The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats

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